TY - JOUR
T1 - Non-coding RNA and gene expression analyses of papillary renal neoplasm with reverse polarity (PRNRP) reveal distinct pathological mechanisms from other renal neoplasms
AU - Nemours, Stéphane
AU - Armesto, María
AU - Arestín, María
AU - Manini, Claudia
AU - Giustetto, Doriana
AU - Sperga, Māris
AU - Pivovarcikova, Kristyna
AU - Pérez-Montiel, Delia
AU - Hes, Ondrej
AU - Michal, Michal
AU - López, José I.
AU - Lawrie, Charles H.
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/6
Y1 - 2024/6
N2 - Papillary renal neoplasm with reversed polarity (PRNRP) is a recently described rare renal neoplasm. Traditionally, it was considered a variant of papillary renal cell carcinoma (PRCC). However, several studies reported significant differences between PRNRP and PRCC in terms of clinical, morphological, immunohistochemical and molecular features. Nonetheless, PRNRP remains a poorly understood entity. We used microarray analysis to elucidate the non-coding RNA (ncRNA) and gene expression profiles of 10 PRNRP cases and compared them with other renal neoplasms. Unsupervised cluster analysis showed that PRNRP had distinct expression profiles from either clear cell renal cell carcinoma (ccRCC) or PRCC cases at the level of ncRNA but were less distinct at the level of gene expression. An integrated omic approach determined miRNA:gene interactions that distinguished PRNRP from PRCC and we validated 10 differentially expressed miRNAs and six genes by quantitative RT-PCR. We found that levels of the miRNAs, miR-148a, miR-375 and miR-429, were up-regulated in PRNRP cases compared to ccRCC and PRCC. miRNA target genes, including KRAS and VEGFA oncogenes, and CXCL8, which regulates VEGFA, were also differentially expressed between renal neoplasms. Gene set enrichment analysis (GSEA) determined different activation of metabolic pathways between PRNRP and PRCC cases. Overall, this study is by far the largest molecular study of PRNRP cases and the first to investigate either ncRNA expression or their gene expression by microarray assays.
AB - Papillary renal neoplasm with reversed polarity (PRNRP) is a recently described rare renal neoplasm. Traditionally, it was considered a variant of papillary renal cell carcinoma (PRCC). However, several studies reported significant differences between PRNRP and PRCC in terms of clinical, morphological, immunohistochemical and molecular features. Nonetheless, PRNRP remains a poorly understood entity. We used microarray analysis to elucidate the non-coding RNA (ncRNA) and gene expression profiles of 10 PRNRP cases and compared them with other renal neoplasms. Unsupervised cluster analysis showed that PRNRP had distinct expression profiles from either clear cell renal cell carcinoma (ccRCC) or PRCC cases at the level of ncRNA but were less distinct at the level of gene expression. An integrated omic approach determined miRNA:gene interactions that distinguished PRNRP from PRCC and we validated 10 differentially expressed miRNAs and six genes by quantitative RT-PCR. We found that levels of the miRNAs, miR-148a, miR-375 and miR-429, were up-regulated in PRNRP cases compared to ccRCC and PRCC. miRNA target genes, including KRAS and VEGFA oncogenes, and CXCL8, which regulates VEGFA, were also differentially expressed between renal neoplasms. Gene set enrichment analysis (GSEA) determined different activation of metabolic pathways between PRNRP and PRCC cases. Overall, this study is by far the largest molecular study of PRNRP cases and the first to investigate either ncRNA expression or their gene expression by microarray assays.
KW - miRNA
KW - papillary renal neoplasm with reversed polarity
KW - pathway analysis
KW - Renal cancer
KW - transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85188211349&partnerID=8YFLogxK
U2 - 10.1016/j.pathol.2023.11.013
DO - 10.1016/j.pathol.2023.11.013
M3 - Article
C2 - 38413252
AN - SCOPUS:85188211349
SN - 0031-3025
VL - 56
SP - 493
EP - 503
JO - Pathology
JF - Pathology
IS - 4
ER -